Elsevier

Biochemical Pharmacology

Volume 42, Issue 2, 5 July 1991, Pages 311-320
Biochemical Pharmacology

Differential effects of recombinant interferon α on constitutive and inducible cytochrome P450 isozymes in mouse liver

https://doi.org/10.1016/0006-2952(91)90718-KGet rights and content

Abstract

The hepatic cytochrome P450 (P450)-dependent monooxygenase system is subject to regulation by a variety of xenobiotics and endogenous factors. During infection and inflammation the P450 system is usually suppressed, but the factors responsible for ihis phenomenon and the P450 isozymes involved have not been identified conclusively. We have studied the effects of a specific inflammatory mediator, recombinant interferon α, on the constitutive and inducible expression of P450 isozymes (from the CYP1A, CYP2B and CYP2C) gene families using isozyme preferred substrates and Western blot analysis. Both increases and decreases in P450 levels occurred in response to interferon α. Suppression of constitutive P450 isozyme expression occurred and was shown to involve a decrease 3n steady-state protein expression. The induction of 7-ethoxyresorufin Odeethylase activity by 3-MC was potentiated whereas induction of 7-pentoxyresorufin- and 7-benzyloxyresorufin O-dealkylases by PB was suppressed by interferon α. These data demonstrate that the effects of interferon α on the P450-dependent monooxygenase system are complex, involving differential regulation of several isozymes. Both direct and indirect mechanisms may participate in these phenomena.

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